A Phase 1/2 Immunotherapy Study of Evofosfamide in Combination with Zalifrelimab and Balstilimab in Patients with Advanced Solid Malignancies

ImmunoGenesis1 site in 1 country71 target enrollmentStarted: January 8, 2025Last updated: January 21, 2025

InterventionsEvofosfamide Zalifrelimab Balstilimab

DrugsEvofosfamide Zalifrelimab Balstilimab

Overview

Phase: Phase 1
Status: Recruiting
Sponsor: ImmunoGenesis
Enrollment: 71
Locations: 1
Primary Endpoint: Incidence and severity of adverse events including dose-limiting toxicities

Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials

Overview

Brief Summary

The purpose of this Phase 1/2 study is to test the overall safety, tolerability, and effectiveness of the combination investigational drugs evofosfamide, zalifrelimab, and balstilimab in treating advanced or metastatic castration-resistant prostate cancer, pancreatic cancer, and human papilloma virus (HPV)-negative squamous cell carcinoma of the head and neck (SCCHN).

Detailed Description

Tumor hypoxia can lead to poor effector T-cell penetration and immunosuppressive signaling via myeloid-derived suppressor cells, myofibroblasts, and regulatory T-cells. Disruption of these hypoxic regions within the tumor microenvironment by the hypoxia-directed cytotoxic agent evofosfamide may enhance the ability of immune checkpoint inhibitors to reject otherwise resistant solid tumors. The hypothesis tested in this study is that evofosfamide, by specifically targeting the hypoxic tumor microenvironment, may enhance the anti-tumor effects of the immune checkpoint inhibitors zalifrelimab (anti-CTLA-4) and balstilimab (anti-PD-1) in select tumors that are generally resistant to therapy.

In the Phase 1 dose escalation part of the study, the maximum tolerated dose (or maximum allowable dose) of evofosfamide in combination with zalifrelimab and balstilimab will be determined. A recommended Phase 2 dose (RP2D) will be determined based on safety and the totality of data.

The Phase 2 dose expansion part of the study will evaluate the Phase 2 dose of the triplet combination in 3 cohorts: 1) patients with locally advanced or metastatic castration-resistant prostate cancer; 2) patients with locally advanced or metastatic pancreatic cancer; and 3) patients with locally advanced or metastatic HPV-negative SCCHN. Each cohort expansion will be carried out independently.

Study Design

Study Type: Interventional
Allocation: Non Randomized
Intervention Model: Sequential
Primary Purpose: Treatment
Masking: None

Eligibility Criteria

Ages: 18 Years to — (Adult, Older Adult)
Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

•Histologically confirmed locally advanced or metastatic castration-resistant prostate cancer, pancreatic cancer, or HPV-negative SCCHN for which no other lines of standard therapy with demonstrated clinical benefit are available or appropriate as treatment.
•Appropriate to enter a clinical trial with a minimum estimated life expectancy of at least 3 months.
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
•Measurable disease as defined by RECIST 1.
•Patients with castration-resistant prostate cancer can have measurable or evaluable disease per PCWG3 criteria. Patients with evaluable disease must have documented evidence of PD as defined by any of the following:
•PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least ≥4.0 ng/mL.
•New or increasing non-bone disease per RECIST 1.1 criteria.
•Positive bone scan with 2 or more new lesions (PCWG3).
•Adequate bone marrow function as defined by the following laboratory test results obtained within 7 days of Cycle 1 Day 1:
•White blood cell count ≥2500 cells/mm

Exclusion Criteria

•A history of currently active/uncontrolled autoimmune diseases or disorders, including inflammatory bowel disease (including Crohn's disease and ulcerative colitis), rheumatoid arthritis, systemic sclerosis (scleroderma), systemic lupus erythematosus, or autoimmune vasculitis (eg, Wegener's granulomatosis).
•Patients with prior history of any Grade 3 or Grade 4 AEs from anti-CTLA-4, anti-PD-1/PD-L1, or anti-CTLA-4 and anti-PD-1/PD-L-1 combination therapy.
•History of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis, or other known risk factors for bowel perforation.
•Patients on long-term systemic steroids (\>10 mg daily prednisone equivalent initiated \>2 weeks prior to study enrollment). Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
•Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study treatment hazardous or obscure the interpretation of AEs, e.g., a condition associated with frequent diarrhea or chronic skin conditions, recent surgery (within 30 days) or colonic biopsy from which the patient has not recovered, partial endocrine organ deficiencies, or substance abuse.
•Concomitant use of QT-prolonging drugs with a risk of causing Torsades de Pointes (TdP).
•History of risk factors for TdP, including family history of long QT syndrome.
•Corrected QT (QTc) interval of ≥470 msec calculated according to Fridericia's formula (QTc=QT/RR \[0.33\]).
•Sustained systolic blood pressure (BP) \>140 mmHg or \<90 mmHg and sustained diastolic BP \>100 mmHg or \<60 mmHg.
•Patients with newly diagnosed, uncontrolled and/or untreated cancer-related central nervous system disease. Patients with treated brain metastases that are radiographically or clinically stable for at least 2 weeks after therapy and have no evidence of cavitation or hemorrhage in the brain lesion(s) are eligible if they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to study enrollment).